--- title: EU GMP Annex 15 Becomes Mandatory for Active Substance Manufacturers description: EU GMP Annex 15 will become mandatory for API manufacturers, strengthening requirements related to qualification, validation, and GMP process control. image: https://blog.pqegroup.com/hubfs/EU%20GMP%20Annex%2015_Blog%20(1).jpg --- [![Logo PQE Group - azzurro - 2024](https://blog.pqegroup.com/hs-fs/hubfs/Logo%20PQE%20Group%20-%20azzurro%20-%202024.png?width=2000&height=721&name=Logo%20PQE%20Group%20-%20azzurro%20-%202024.png "Logo PQE Group - azzurro - 2024")](https://www2.pqegroup.com) - [Home](https://www2.pqegroup.com/) - [Industry](https://www2.pqegroup.com/industry/) - [Pharma & API](https://www2.pqegroup.com/pharma-api/) - [Medical Device](https://www2.pqegroup.com/medical-device/) - [Biotech](https://www2.pqegroup.com/biotech/) - [Startup](https://www2.pqegroup.com/startup/) - [Veterinary](https://www2.pqegroup.com/veterinary/) - [Services](https://www2.pqegroup.com/services/) - [Data Integrity](https://www2.pqegroup.com/data-integrity/) - [Digital Governance](https://www2.pqegroup.com/digital-governance/) - [Engineering](https://www2.pqegroup.com/engineering/) - [Commissioning, Qualification and Validation (CQV)](https://www2.pqegroup.com/commissioning-qualification-validation/) - [Quality Compliance](https://www2.pqegroup.com/quality-compliance/) - [Laboratory Excellence](https://www2.pqegroup.com/laboratory-excellence/) - [Regulatory Affairs](https://www2.pqegroup.com/regulatory-affairs/) - [Audits](https://www2.pqegroup.com/audits/) - [Training](https://www2.pqegroup.com/training/) - [Clinical Research](https://www2.pqegroup.com/clinical-research-services/) - [Pharmacovigilance](https://www2.pqegroup.com/pharmacovigilance/) - About - [About Us](https://www2.pqegroup.com/about/) - [ESG](https://www2.pqegroup.com/about/csr/) - [Women in STEM](https://www2.pqegroup.com/about/women-in-stem/) - Resources - [News & Press](https://www2.pqegroup.com/news/) - [Webinars](https://www2.pqegroup.com/webinars/) - [Blog](https://blog.pqegroup.com/) - [Careers](https://www2.pqegroup.com/careers/) - [Contact Us](https://www2.pqegroup.com/contact-us/) ![](https://blog.pqegroup.com/hubfs/blank-user.png) Ana Franco CQV Operations Manager @PQE Group # **EU GMP Annex 15 Becomes Mandatory for Active Substance Manufacturers** [Commissioning, Qualification and Validation (CQV)](https://blog.pqegroup.com/tag/commissioning-qualification-and-validation-cqv) Did you know that EudraLex Volume 4. “Good Manufacturing Practices for medicinal products for human and veterinary Annex 15 Qualification and Validation”, will soon become mandatory for API manufacturers?   Significant changes are coming to Qualification and Validation in the Pharma industry. While EU Annex 15 has traditionally been considered optional for active substance manufacturers, its principles have long been broadly acknowledged and applied across the sector. Now, the European Medicines Agency (EMA), together with PIC/S, has proposed a specific revision of the EU GMP Annex 15, moving from an optional guideline to a mandatory requirement for manufacturers of active substances. With implementation planned for December 2026, the transition period has already begun, and this is the moment for API manufacturers to start preparing. ## **What Is Expected Under the New Annex 15?  ** The updated Annex 15 is expected to strengthen public health protection by encouraging API manufacturers to maintain greater process oversight, deeper product knowledge, and more robust control strategies. Although Annex 15’s update from optional to mandatory will not anticipate critical business impact, regulatory bodies emphasize the importance of appropriate stakeholder consultation during the transition. The application of effective Quality Risk Management tools and principles throughout the life cycle of a product, including validation and qualification activities, leads to better, more informed, and timely decisions.   ## **What Changes Are Proposed in the new version of Annex 15 GMP? ** The revision proposes expanding the scope of Annex 15 to fully include active substance (AS) manufacturers, and updating the text in several key areas to better align it with EudraLex Volume 4, Part II, as well as other guidance documents relevant to active substances (including GDPs). The main updates include: - Strengthening the Validation Master File, Qualification & Validation Policy, and Change Control, improving how AS manufacturers document validation activities. - Increasing oversight of third‑party validation to enhance control over outsourced activities. - Reinforcing the need to investigate results that fall outside acceptance criteria, supporting deeper process understanding. - In order to have maximum control over the qualification process, extend the use of the initial phases of URS and link them to the qualification stages themselves (DQ, IQ, OQ, PQ). - Emphasizing robust process development, clearer concurrent validation expectations and added guidance on process validation, including recovery of materials and solvents. - Emphasis in stronger supplier qualification, - Providing more guidance on GDP for active substances, especially around transport verification, and emphasizing how transport can impact AS quality.   ## **Why You Should Prepare Now ** The public consultation will end soon, and the final draft is expected to be ready by the end for the year, therefore it is now strategically important to prepare proactively. Preparing in advance allows you to: - Strengthen internal systems before the guideline comes into effect - Avoid last‑minute compliance gaps - Improve quality and transparency - Mitigate inspection risk ahead of the deadlines At PQE Group, we have the expertise and global experience to support you through this transition and ensure full compliance with the new version of EU GMP Volume 4 Annex 15.   **Source:**  European Medicines Agency (EMA), 2026. *Concept paper on the revision of the guidelines on Good Manufacturing Practice for medicinal products – Annex 15: Qualification and Validation*: [https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-revision-guidelines-good-manufacturing-practice-medicinal-products-annex-15-qualification-validation\_en.pdf](https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-revision-guidelines-good-manufacturing-practice-medicinal-products-annex-15-qualification-validation_en.pdf)   ![EU GMP Annex 15_Blog](https://blog.pqegroup.com/hs-fs/hubfs/EU%20GMP%20Annex%2015_Blog.jpg?width=2000&name=EU%20GMP%20Annex%2015_Blog.jpg) ## Need expert support for equipment validation? PQE Group offers a wide range of [Commissioning, Qualification & Validation (CQV) services](https://www2.pqegroup.com/commissioning-qualification-validation/) to ensure that your manufacturing processes are efficient, reliable, and meet regulatory authority standards. Our cutting-edge, integrated approach ensures that all tools used in your manufacturing processes have a significant impact on product quality. 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